Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl-benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids

A series of berberine-phenyl-benzoheterocyclic (26-29) and tacrine-phenyl-benzoheterocyclic hybrids (44-46) were synthesised and evaluated as multifunctional anti-Alzheimer's disease agents. Compound 44b, tacrine linked with phenyl-benzothiazole by 3-carbon spacers, was the most potent AChE inhibitor with an IC50 value of 0.017 mu M. This compound demonstrated similar A beta aggregation inhibitory activity with cucurmin (51.8% vs 52.1% at 20 mu M, respectively), indicating that this hybrid is an excellent multifunctional drug candidate for AD. (C) 2012 Elsevier Ltd. All rights reserved.